Vitamin A antibiotic could be new superbug killer, finds study

Alex Matthews-King

A new type of antibiotic has been discovered that could be a potent new weapon for tackling drug-resistant bacteria, particularly recurring infections that pose a serious risk to people with cystic fibrosis.

Two chemical compounds from the same family as vitamin A, a group known as retinoids, have been identified by US researchers as a potential weapon against drug-resistant superbugs, including hospital infection MRSA.

These chemicals have not been considered useful before because they are also poisonous to human cells, however the team – including researchers from Brown and Harvard Universities – were able to modify it to be safe.

“The molecule weakens the cell membranes of bacteria, but human cells also have membranes,” said Professor William Wuest, associate professor of chemistry at the Emory University Antibiotic Resistance Centre and one of the authors of the study, published in the journal Nature.

“But we found a way to tweak the molecule so that it now selectively targets bacteria”.

This technique could mean thousands of other compounds which are currently too toxic to humans could be potential avenues for future drugs.

Identifying another new class of antibiotic, the second in as many months, is another step to overturning a decades-long drought in new antibiotics being brought to clinics and could help avert a “post-antibiotic apocalypse”.

The new compounds could be particularly potent in treating chronic infections because the researchers showed they have the unprecedented power to kill dormant “persister” cells – bacteria which have become inactive and are more resistant to antibiotics.

These bacteria become embedded in “bio films” in the lungs of cystic fibrosis patients, or on implanted medical devices like pacemakers, and can reignite infections after they’ve been treated.

In this form, surgery is often the only treatment as aggressive antibiotic treatment can make the problem of drug resistance even worse as the infection regrows from the most resilient bacteria.

The team proved their drug could work safely in a living organism by testing it in MRSA-infected mice.

MRSA is the major superbug responsible for hundreds of thousands of life-threatening infections in hospital intensive care units around the world each year, due in part to its resilience against persister cells.

“The results were extremely positive. We are extremely optimistic,” said Professor Eleftherios Mylonakis, chief of infectious diseases at Rhode Island Hospital.

But he warned the development from being a promising candidate into a functional drug which can be trialled in humans was still many years away and that more investment was needed in both the initial discovery and development of new drugs.

In this study, researchers tested 82,000 compounds, and identified 185 that looked promising before ending up with the two retinoid compounds, and now they will need large animal and human trials to test a future drug.

“This is an emergency, by 2050, superbugs will surpass cancer as the global number one killer,” Professor Mylonakis said.

“This is a frightening situation. It affects more than individuals in the hospital or the very ill or the very old. It affects everybody.”

Independent researchers said the benefits in tackling persister cells were “remarkable”.

Dr Julian Hurdle of the Centre for Infectious and Inflammatory Diseases at Texas A&M University said: “In experiments in mice, [the treatment] remained in circulation in the animals’ bodies for several hours at high enough concentrations to kill MRSA persister cells, but did not give rise to signs of toxicity such as liver or kidney damage.

“Remarkably, the authors showed in mice it could tackle what would generally be considered to be a treatment-resistant form of MRSA.”

Siouxsie Wiles, associate professor of microbiology at the University of Auckland, said the authors’ findings didn’t show a complete wipe-out of bacteria, but the drug made a significant dent and could one day become a new drug treatment.

She added: “What stands out to me about the study is the elegant way the researchers identified the new compounds – infecting microscopic worms with MRSA and then adding compounds to see if any of them helped the worms survive being infected.”